静脉注射途径移植骨髓基质细胞的特点

目的:探讨在大鼠脑缺血的情况下经尾静脉注射移植骨髓基质细胞的可行性,为骨髓基质细胞脑移植治疗提供一种简捷、安全、有效的途径。方法:实验于2005-10/2006-08在北华大学医学院实验中心完成。取1～2个月龄SD大鼠双侧股骨和胫骨,体外分离培养大鼠骨髓基质细胞。取体质量为280～320g的SD大鼠25只,采用颈内动脉线栓法制作大脑中动脉梗死模型,造模成功后在25只大鼠中随机盲抓分为2组:骨髓基质细胞移植组(n=15)、对照组(n=10)。骨髓基质细胞移植组经静脉缓慢推入含Hoeschst33342标记的骨髓基质细胞细胞悬液1mL(2.0×107个细胞),对照组用同样方法经尾静脉注入等量不含骨髓基质细胞的DMEM培养液作为对照。分别于移植后1d、7d、14d时间点对两组大鼠进行神经功能损害严重程度评分及大脑组织切片观察比较。结果:25只大鼠均进入结果分析。①各代细胞90%以上表达巢蛋白阳性。②与对照组相比,骨髓基质细胞移植组大鼠运动、神经功能恢复明显[骨髓基质细胞移植组:(6.10±2.96),(3.30±1.83),(2.10±1.20)分;对照组:(7.43±1.51),(6.14±1.35),(4.43±1.40)分,P<0.05]。③骨髓基质细胞移植组大鼠脑组织结构较清晰、完整;对照组大鼠脑组织破坏溶解,组织结构松散,细胞结构不完整,胞浆疏松,染色变浅,间质水肿。结论:通过静脉注射进行骨髓基质细胞移植,方法简便、安全,对神经损伤动物组织重建及神经功能有确切的修复效果。     

Ruxolitinib partially reverses functional natural killer cell deficiency in patients with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations

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A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin''s lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody–drug conjugates (ADCs) exhibited subnanomolar IC₅₀ values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs.     

All Aspects of Health Literacy Scale (AAHLS): Developing a tool to measure functional,communicative and critical health literacy in primary healthcare settings

Objective

Our aim was to develop and pilot a tool to measure health literacy in primary health care settings, encompassing functional, communicative and critical health literacy.

Methods

Following consultation with providers and users of primary health care we developed a fourteen-item self-report scale, which was piloted on 146 participants. The reliability, content and construct validity of the scale was investigated as well as relationships between scores on the scales and participant characteristics.

Results

The overall scale had adequate reliability (Cronbach's alpha = 0.74), though reliability of the subscales was less consistent. Principal component analysis indicated that scale items loaded on four factors, corresponding to skills in using written health information; communicating with health care providers; health information management and appraisal assertion of individual autonomy with regards to health. Overall scores and different subscale scores were associated with ethnic minority status, educational level, and self-rated health status, though the picture was complex.

Conclusion

Health literacy is a complex and evolving construct. Nevertheless, we succeeded in developing a brief measure relating to different health literacy competencies, beyond functional literacy skills.

Practice implications

Assessment using the AAHLS can provide important information for health care practitioners about the health literacy needs and capabilities of service users.     

Modelling the lung function of Caucasians during adolescence as a basis for reference values

Background: In childhood the relationship between lung size and stature changes during the adolescent growth spurt. This is not allowed for in models of lung function based on stature alone. For spirometric indices inclusion of an age?×?stature interaction (A?×?St) can overcome the difficulty. Aim: The study tested the hypothesis that this simple, interactive model might also be effective for total lung capacity and its subdivisions and the single breath transfer factor for carbon monoxide. Subjects and methods: Data were available for 695 asymptomatic non-smokers (Caucasians) aged 7–20 years (440 boys, 255 girls). Each lung function index was described using the above model and the fit was compared with that from a linear, power or polynomial model based on stature alone. Results: After allowing for stature, the A?×?St interaction term was significant for almost all indices. The improved fit was most apparent for the lung function of older adolescent boys. Reference values using the model are reported. Conclusions: A simple model based on stature and an interaction between stature and age can account for the changing relationship between body habitus during the growth spurt and lung size and transfer factor in a single equation encompassing children and adolescents. Its use is recommended for deriving reference values when the explanatory variables are limited to stature and age.

Résumé. Arrière plan: Les modèles de fonction pulmonaire établis à partir de la seule stature, ne tiennent pas compte du fait que la relation entre taille des poumons et stature évolue au cours de la poussée de croissance de l’adolescence. Cette difficulté peut être surmontée en incluant l’interaction age × stature (A?×?St) dans les indices spirométriques.

But: Cette étude teste l’hypothèse que ce modèle interactif simple pourrait aussi être efficace pour la capacité pulmonaire totale et ses subdivisions ainsi que pour le facteur de transfert de monoxyde de carbone d’une simple expiration.

Sujets et méthodes: Des données ont été réunies sur 695 non fumeurs caucasiens asymptomatiques, âgés de 7 à 20 ans (440 garçons et 255 filles). Chaque indice de fonction pulmonaire a été décrit en utilisant le modèle ci-dessus et l’ajustement a été comparé à celui d’un modèle linéaire, puissance ou polynomial, fondé sur la seule stature.

Résultats: Après contrôle de la stature, le terme d’interaction (A?×?St) est significatif pour presque tous les indices. L’amélioration de l’ajustement est plus particulièrement notable pour la fonction pulmonaire des garçons adolescents les plus âgés. On reporte les valeurs de référence utilisant le modèle.

Conclusion: Un simple modèle fondé sur la stature et sur l’interaction entre stature et âge peut rendre compte du changement du rapport entre la conformation corporelle au cours de la poussée de croissance, la taille des poumons et facteur de transfert, par une simple équation regroupant enfants et adolescents. Son usage est recommandé pour extraire des valeurs de référence lorsque les variables explicatives sont limitées à la stature et à l’âge.

Zusammenfassung. Hintergrund: In der Kindheit ändert sich die Relation von Lungengröße und Körperhöhe während des pubertären Wachstumsschubes. Dem wird in Lungenfunktionsmodellen, die allein auf Körperhöhe basieren, nicht Rechnung getragen. Für die spirometrischen Indizes kann die Schwierigkeit durch Einführung einer Alter?×?Körperhöhen-Interaktion behoben werden.

Ziel: Die Studie untersuchte die Hypothese, dass dies einfache, interaktive Modell auch für totale Lungenkapazität und weitere atemmechanische Parameter und den CO-Transfer-Faktor (sogenannte “Diffusionskapazität”) in der Ein-Atemzug-Methode gültig sein könnte.

Probanden und Methoden: Es waren Daten für 695 asymptomatische 7-20-jährige Nichtraucher kaukasischer Herkunft (440 Knaben, 255 Mädchen) verfügbar. Jeder Lungenfunktionsindex wurde nach obigem Modell beschrieben, und die Güte der Kurvenanpassung wurde mit derjenigen verglichen, die sich aus einem linearen, exponentiellen oder polynomischen Modell auf der Basis von Körperhöhe allein ergibt.

Ergebnisse: Nach Korrektur für Körperhöhe wurde der Terminus Alter?×?Körperhöhen-Interaktion für fast alle Indizes signifikant. Die verbesserte Anpassung war besonders offensichtlich für die Lungenfunktion älterer männlicher Jugendlicher. Es werden Referenzwerte auf der Basis dieses Modells angegeben.

Zusammenfassung: Ein einfaches Modell auf der Basis von Körperhöhe und einer Interaktion zwischen Körperhöhe und Alter kann der wechselnden Beziehung zwischen der körperlichen Konstitution im Verlauf des Wachstumsschubes und der Lungengröße und einem Transfer-Faktor in einer einzigen Gleichung Rechnung tragen, die gleichermaßen Kinder und Jugendliche einschließt. Die Verwendung des Modells ist empfehlenswert, um Referenzwerte abzuleiten, sobald sich die Bezugsgrößen auf Körperhöhe und Alter beschränken.

Resumen. Antecedentes: Durante la infancia, la relación entre el tamaño pulmonar y la estatura cambia durante el estirón puberal. Este hecho no se tiene en cuenta en los modelos de la función pulmonar basados únicamente en la estatura. La inclusión de una interacción entre la edad y la estatura (A?×?St) en los índices espirométricos, puede vencer esta dificultad.

Objetivo: El estudio comprobó la hipótesis de que este simple modelo interactivo también podría ser efectivo para la capacidad pulmonar total y sus subdivisiones, así como para la capacidad de difusión (factor de transferencia) de monóxido de carbono mediante respiración única.

Sujetos y métodos: Se disponía de datos de 695 no fumadores asintomáticos (caucásicos) de entre 7 y 20 años de edad (440 chicos, 255 chicas). Cada índice de la función pulmonar fue descrito utilizando el modelo señalado arriba y el ajuste se comparó con el de un modelo linear, potencial o polinómico, basado únicamente en la estatura.

Resultados: Después de tener en cuenta la estatura, el término de interacción A?×?St fue significativo en casi todos los índices. El ajuste mejorado fue más aparente para la función pulmonar de los chicos adolescentes de más edad. En el trabajo se muestran los valores de referencia.

Conclusiones: Un modelo simple basado en la estatura y una interacción entre la estatura y la edad pueden explicar la relación variable entre la estatura durante el estirón de crecimiento, el tamaño pulmonar y el factor de transferencia, en una ecuación simple que incluye niños y adolescentes. Se recomienda su utilización para derivar valores de referencia cuando las variables explicativas son únicamente la estatura y la edad.     

Comparison of efficacy of three commercially available dentifrices on dentinal hypersensitivity: a randomized clinical trial

Background: Dentinal hypersensitivity has been defined as a short, sharp pain arising from exposed dentine as a result of various stimuli such as heat, cold, chemical, or osmotic, that cannot be ascribed to any other pathology. This study was conducted to assess the efficacy of three commercially available toothpastes in the reduction of dentinal hypersensitivity. Methods: A total of 149 subjects (72 males and 77 females; aged 20 to 60 years) were entered into the study and randomly divided into four groups: Group 1 – toothpaste containing 5% potassium nitrate; Group 2 – toothpaste containing 5% calcium sodium phosphosilicate with fused silica; Group 3 – toothpaste containing 3.85% amine fluoride; and Group 4 – a placebo toothpaste. After sensitivity scores for controlled air stimulus and cold water at baseline were recorded, subjects were given toothpastes and sensitivity scores were measured again at 2 weeks and 6 weeks. Results: All groups showed a reduction in sensitivity scores at 2 weeks and 6 weeks. The calcium sodium phosphosilicate group was found to be significantly better compared to the other groups at the end of 6 weeks. Conclusions: The calcium sodium phosphosilicate group showed a better reduction in the symptoms of dentinal hypersensitivity.     

A novel treatment of childhood lymphoblastic non-Hodgkin's lymphoma: early and intermittent use of teniposide plus cytarabine

We treated 24 children and adolescents with stage III or IV lymphoblastic non-Hodgkin's lymphoma, using a protocol designed for patients with poor-prognosis acute lymphoblastic leukemia (ALL). Early therapy consisted of teniposide plus cytarabine administered before and immediately after prednisone, vincristine, and asparaginase. The two- drug combination was also given intermittently with continuous 6- mercaptopurine and methotrexate during the first year of continuation chemotherapy. Periodic intrathecal methotrexate and delayed cranial irradiation were used to prevent central nervous system involvement. Anthracycline compounds, alkylating agents, high-dose methotrexate, and involved-field irradiation were not used in any phase of treatment. Twenty-two (96%) of the 23 evaluable patients achieved complete remission. With a median follow-up of 2 1/2 years, only four patients have relapsed; the remainder have been disease-free for eight months to more than five years. The projected four-year continuous complete remission rate is 73% for all patients and 79% for the 19 with mediastinal involvement at diagnosis. These results demonstrate that use of teniposide plus cytarabine with an otherwise conventional plan of ALL therapy is an effective approach to the treatment of childhood lymphoblastic lymphoma.     

Selective accumulation of virus-specific CD8+ T cells with unique homing phenotype within the human bone marrow

The bone marrow plays a unique role within the immune system. We compared the phenotype and function of virus-specific CD8(+) T cells from matched samples of human peripheral blood and bone marrow. Analysis of virus-specific memory CD8(+) T cells showed widely divergent partition of antigen-specific populations between blood and bone marrow. T cells specific for Epstein-Barr virus (EBV) lytic antigens were enriched 3-fold in marrow compared with blood, whereas the response to EBV latent epitopes was equivalent between the 2 compartments. No difference in EBV viral load or expression of the EBV lytic protein was observed between blood and bone marrow. In direct contrast, although cytomegalo-virus (CMV)-specific T cells were the largest virus-specific population within peripheral blood, they were reduced by 60% within marrow. Bone marrow T cells were found to exhibit a unique CCR5(+)CXCR6(+)CXCR3(-) homing phenotype which has not been observed on T cells from other secondary lymphoid organs or peripheral organs. Expression of CCR5 and CXCR6 was higher on EBV-specific T cells within peripheral blood compared with CMV-specific populations. These observations identify a novel bone marrow homing phenotype for CD8(+) memory T cells, which necessitates a reevaluation of the magnitude of antigen-specific populations within the lymphoid system.